In a presentation at the recent NAMS Congress, an analysis by Pinkerton and colleagues highlighted the effect of hormone therapy (HT) on hot flushes in women, regardless of their age or age at start of therapy. This was a post hoc analysis of data retrieved from five phase-3 trials (SMART trials), which gave the clinical basis for approval of the combination of conjugated estrogens and bazedoxifene back in 2013. These clinical trials included 3168 women in the HT arms (either CEE at 0.45 mg or 0.625 mg, plus 20 mg bazedoxifene) and 1241 women in the placebo arm. The focus of this new analysis was to determine whether the effects of the combination would differ, depending on when it was started in relation to menopause. Most of the women in the SMART trials were 40–75 years of age, white, and postmenopausal. Years since menopause ranged from 1 to 35 years, but the mean range was approximately 4–8 years. The analysis showed that menopausal symptoms improved to a similar degree, regardless of whether a woman started taking the combination less than 5 years after the start of menopause or more than 5 years after. Dr Pinkerton concluded that, whether the women started taking the combination sooner or later, there were no discernable differences in the reduction in bothersome hot flushes, prevention of bone loss, improvement in sleep, improvement in quality of life, or improvement in vulvovaginal changes.

Comment

Postmenopausal HT is primarily indicated for the treatment of hot flushes. Years ago, when HT was prescribed at any postmenopausal age with almost no restrictions, things were very clear: if a woman suffes menopausal symptoms, HT would be her most effective, easy and practical solution. However, the WHI study raised awareness to the downside of HT, the adverse effects and risks, which were found to be pronounced mainly in women who were late-starters of HT. As a result, the questions whether to start therapy years after menopause in symptomatic women, or whether therapy be continued after a certain period of use, have become a major issue nowadays. People may forget that the data from the WHI clinical trial in regard to relief of hot flushes actually provided favorable relevant information [1]. The mean age of the whole WHI cohort was 63 years, with age range 50–79 years. Most participants had never used HT before; about two-thirds were menopausal for more than 10 years at baseline, and about 17% of the total cohort reported having moderate to severe hot flushes. Although not clearly shown in the article, it can be assumed that most women with hot flushes were late-starters of HT. At the 1 year follow-up, 76.7% of the women in the estrogen-plus-progestin group had improvement in the severity of hot flushes, as compared with 51.7% of the women in the placebo group (p < 0.001).

SMART phase-3 studies have already published their data on efficacy in alleviating hot flushes [2]. Overall, the combination significantly reduced the frequency and severity of hot flushes compared to placebo. But now it seems that we are re-inventing the wheel: we want to be re-assured that HT started in elderly women suffering from bothersome hot flushes is really effective. Perhaps the new hormonal preparation, which included conjugated estrogen with a SERM, rather than the traditional estrogen–progestin combination, was the real reason for the post hoc analysis. In any case, we may rest assured that the approval of HT for the indication of vasomotor symptoms was rightly given, and that age is not a limiting factor. Still, in line with current debates and cautions in prescribing hormones, Dr Pinkerton was quoted in Medscape as follows: 'We're not saying that hormone therapy – whether it is traditional or this new combination – should be started after age 60, or more than 10 years out from menopause, we are just saying that, whether you are within that first 5 years when symptoms are often more severe, or out 5 years, it's effective.'